Safety Study of SMOFlipid to Evaluate the Risk of Developing EFAD and/or PNAC in Pediatric and Adult Patients

Malnutrition Clinical Trial

Official title:

A Single-arm Open-label Safety Study of SMOFlipid to Evaluate the Risk of Developing Essential Fatty Acid Deficiency (EFAD) and/or Parenteral Nutrition-associated Cholestasis (PNAC) in Pediatric Patients 1 Month to 17 Years of Age and in Adult Patients, Who Are Anticipated to Need 8 Weeks or Longer of Parenteral Nutrition Treatment

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06049680
• Other study ID #: SMOF-044-CP4 (PMR 4240-1)
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2024
• Est. completion date: September 2026

Study information

• Verified date: September 2023
• Source: Fresenius Kabi
• Contact: Cornelia Schneider-Schranz, PhD
• Phone: +49 6172 608
• Email: Cornelia.Schneider-Schranz[@]fresenius-kabi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the risk of developing EFAD and/or PNAC in adult and pediatric patients 1 month of age and older, who are anticipated to need 8 weeks or longer of parenteral nutrition treatment with SMOFlipid.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: September 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

Age Limits: and Adults

Inclusion Criteria:

1. Male or female patients, at least 1 month of age.

2. Patients who require PN for at least 5 days/week.

3. Patients who receive 80% or more of their total energy requirements as PN at enrollment and who are expected to receive 80% or more of their total energy requirements as PN for at least 56 days.

4. Written informed consent. In case of pediatric patients, informed consent must be obtained from parent(s) or legal representatives. If possible, the assent of the pediatric patient must also be obtained (according to local law).

Exclusion Criteria:

1. Use of any other lipid injectable emulsion than SMOFlipid within 6 months prior to study participation

2. Known hypersensitivity to fish, egg, soybean, or peanut proteins, or to any of the active ingredients or excipients of SMOFlipid.

3. Hyperlipidemia or disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration >250 mg/dL in infants or >400 mg/dL in older pediatric and adult patients).

4. Inborn errors of amino acid metabolism.

5. Cardiopulmonary instability (including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis and hemodynamic instability requiring significant vasopressor support).

6. Hemophagocytic syndrome.

7. Liver enzymes (either AST, or ALT, or GGT) exceeding 2 x upper limit of normal range

8. Direct bilirubin exceeding 2 x upper limit of normal range

9. INR exceeding 2 x upper limit of normal range and patient not receiving oral anticoagulants.

10. Any known hepatic condition outside of IFALD that will increase direct bilirubin =2.0 mg/dL.

11. Clinically significant abnormal levels of any serum electrolyte (sodium, potassium, magnesium, calcium, chloride, phosphate).

12. Active bloodstream infection demonstrated by positive blood culture at screening.

13. Severe renal failure (eGFR <15 ml/min per 1.73 m2) including patients on renal replacement therapy.

14. Abnormal blood pH, oxygen saturation, or carbon dioxide.

15. Pregnancy or lactation.

16. Participation in another interventional clinical study.

17. Unlikely to survive longer than 56 days.

Related Conditions & MeSH terms

• Child Nutrition Disorders
• Malnutrition
• Malnutrition, Child

Intervention

Drug:
• SMOFlipid® (lipid injectable emulsion)
SMOFlipid is a sterile, nonpyrogenic, white, homogenous lipid emulsion for intravenous infusion. The lipid content of SMOFlipid is 0.20 g/mL, and comprises a mixture of soybean oil, MCT, olive oil, and fish oil. SMOFlipid belongs to the pharmacotherapeutic group: "Solutions for parenteral nutrition, fat emulsions" (ATC-code: B05BA02). SMOFlipid is indicated in adult and pediatric patients, including term and preterm neonates, as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Locations

Country	Name	City	State
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Fresenius Kabi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of PNAC	defined as direct bilirubin level > 2 mg/dL, confirmed by a second sample collected 7 days after the first sample	Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Primary	Time to direct bilirubin > 2mg/dL	(confirmed by a second sample collected 7 days after the first)	Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Primary	Incidence of EFAD	Triene/tetraene ratio in total plasma to assess EFAD (Holman 1960), Severity of EFAD will be graded based on triene/tetraene ratio, as suspected = 0.05, moderate = 0.20 and severe = 0.40 (Cober et al 2012)	Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Primary	Incidence of clinical EFAD		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Primary	Fatty acids	analyzed in total plasma, including linoleic acid, a-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid	Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: triglycerides		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: direct bilirubin		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: total bilirubin		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: alanine aminotransferase (ALT)		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: aspartate aminotransferase (AST)		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: gamma-glutamyl transferase (GGT)		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: alkaline phosphatase (ALP)		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: creatinine		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: urea nitrogen		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: electrolytes		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: glucose		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values: total protein		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values hematology: white blood cell count (WBC), red blood cell count (RBC), and platelet count		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values hematology: Hemoglobin		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values hematology Hematocrit		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Laboratory values hematology: International normalized ratio		At baseline before start of treatment to assess eligibility
Secondary	Vital signs: Blood pressure		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Vital signs: Heart rate		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Vital signs: Body temperature		Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	Incidence of adverse events		Start of Treatment until After End of Last Study PN (+6 months for pediatric patients). Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).
Secondary	BMI	BMI is the weight in kilograms divided by height in meters squared. Alternatively, BMI can be calculated by dividing the weight in kilograms by the height in centimeters squared, and then multiplying the result by 10,000.	Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days).